Protective effect of peptide leukotriene antagonist on renal failure induced by a tourniquet in rabbits.

Abstract

We studied the effects of a selective antagonist of peptide leukotriene D4/E4 (LY-171883) and 5-lipoxygenase inhibitor diethylcarbamazine (DEC) in renal failure induced by a tourniquet, because peptide leukotrienes (LTs) were suggested to play a key role in our previous study. The hind limbs of anesthetized rabbits were fastened for 5 h and then released for 6 h. LY171883 (4 mg/kg/h) and DEC (40 mg/kg/h) were administered via the aural vein from 30 min before the tourniquet and during the experiment in each tourniquet group. The tourniquet induced renal injuries represented by increases in serum BUN and creatinine, and the injuries in the fastened muscles represented increases in serum CPK and edema index of the fastened site. LY171883 and DEC significantly attenuated the aggravation of the renal functions induced by a tourniquet when compared with the vehicle-treated group. LY171883 did not affect the injuries in the fastened muscles, but DEC attenuated it significantly when compared with the vehicle-treated group. The protection of peptide LT antagonist and 5-lipoxygenase inhibitor in the tourniquet-induced renal failure elucidate that peptide LTs trigger renal failure induced by a tourniquet.